• Title/Summary/Keyword: Systemic administration

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Recent Advancements of Treatment for Leptomeningeal Carcinomatosis

  • Gwak, Ho-Shin;Lee, Sang Hyun;Park, Weon Seo;Shin, Sang Hoon;Yoo, Heon;Lee, Seung Hoon
    • Journal of Korean Neurosurgical Society
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    • v.58 no.1
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    • pp.1-8
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    • 2015
  • Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

Induction of a systemic IgG and secretory IgA responses in mice by peroral immunization with uropathogenic Escherichia coli adhesin protein coupled to cholera toxin A2B subunits

  • Lee, Yong-Hwa;Kim, Byung-Oh;Rhee, Dong-Kwon;Pyo, Suh-Kneung
    • Biomolecules & Therapeutics
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    • v.11 no.3
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    • pp.157-162
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    • 2003
  • The generation of secretory IgA antibodies(Abs) for specific immune protection of mucosal surfaces depends on stimulation of the mucosal immune system, but this is not effectively achieved by parenteral or even oral administration of most soluble antigens. Thus, to produce a possible vaccine antigen against urinary tract infections, the uropathogenic E. coli (UPEC) adhesin was genetically coupled to the ctxa2b gene and cloned into a pMAL-p2E expression vector. The chimeric construction of pMALfimHIctxa2b was then transformed into E. coli K-12 TB1 and its nucleotide sequence was verified. The chimeric protein was then purified by applying the affinity chromatography. The purified chimeric protein was confirmed by SDS-PAGE and western blotting using antibodies to the maltose binding protein (MBP) or the cholera toxin subunit B (CTXB), plus the N-terminal amino acid sequence was analyzed. The orderly-assembled chimeric protein was confirmed by a modified $G_{M1}$-ganglioside ELISA using antibodies to adhesin. The results indicate that the purified chimeric protein was an Adhesin/CTXA2B protein containing UPEC adhesin and the $G_{M1}$-ganglioside binding activity of CTXB. This study also demonstrate that peroral administration of this chimeric immunogen in mice elicited high level of secretory IgA and serum IgG Abs to the UPEC adhesin. The results suggest that the genetically linked CTXA2B acts as a useful mucosal adjuvant, and that the adhesin/CTXA2B chimeric protein might be a potential antigen for oral immunization against UPEC.

Enhanced Controlled Transdermal Delivery of Hydrochlorothiazide from an Ethylene-vinyl Acetate Matrix

  • Kim, Dal-Keun;Park, Jung-Chan;Chang, Ik-Hyun;Kang, Chung;Ryu, Sang-Rok;Shin, Sang-Chul
    • Journal of Pharmaceutical Investigation
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    • v.40 no.3
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    • pp.167-173
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    • 2010
  • Repeated oral administration of hydrochlorothiazide, a loop diuretic, due to transient high blood levels, may cause adverse effects such as gastric disturbance, nausea, high blood sugar, and hyper lipidemia. Transdermal administration could avoid some of these systemic side effects and gastric disorders. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of hydrochlorothiazide. Drug solubility was highest at 40% PEG-400 volume fraction. Drug release increased as concentration increased with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy, measured from the slope of log P versus 1000/T, was 11.9 kcal/mol for a 2.5% loading dose from EVA matrix. Diethyl phthalate had the highest plasticizing effects on the release of hydrochlorothiazide. To increase the skin permeation of hydrochlorothiazide from the EVA matrix, enhancers such as the saturated fatty acids, the unsaturated fatty acids, and the non-ionic surfactants were added to the EVA matrix, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Polyoxyethylene 23-lauryl ether showed the highest enhancing effects. In conclusion, transdermal delivery of hydrochlorothiazide could be improved from an EVA matrix containing plasticizer and permeation enhancer.

A Clinical Review of Surgically Treated 115 Cases of Lung Abscess (외과적 치료를 가한 폐농양 115례에 대한 임상적 관찰)

  • 문한배;이호일
    • Journal of Chest Surgery
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    • v.2 no.1
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    • pp.3-12
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    • 1969
  • Prior to availability of antibiotics, lung abscess has been recognized as one of the most serious pulmonary disease, and despite of diminished morbidity and mortality rate with the advent of antibiotics and development of better technique in the fields of surgery on pulmonary disease it continues to be a virulent form of pulmonary supuration. It is the purpose of this paper to present a clinical review of 115 lung abscess treated by surgically at "The National Medical Center" during past 9 years. 1. The most common age of occurrence is between the age of 30 and 50, and 105 cases were male and 31 cases occurred in female. 2. Numerous etiological factors may play a role in the formation of a pulmonary abscess; aspiration in 36 patients of which 2 patients had diabetes, 54 patients had preceding URI or pneumonia, and 5 patients followed liver abscess, one of which in hematogenous route. In 20 patients, no predisposing factor could be determined- 3. Clubbing digits were presented in 26 of 1315 patients suggesting chronicity of the disease, and gastric ulcer were combined in 3 of 136 patints. 4. Apparently the onset was insidious, and the progress was masked by indiscriminate administration of antibiotics for URI and TB remedies under impression of pul. tbc. Previous TB treatments were done in 56.%[76 cases] for one week to two years and administration of antibiotics in 51 cases. 5. 89 cases were on tbe right and 2t5 cascs were on the left side. 51 cases of pneumonectomy and 8 of open drainage, of which 4 of Monaldi procedure, were made and operative mortality rate was 5.2%. Numerous complications such as 8 of empyema, 4 of each bleeding and atelectasis, 2 of BPF, 1 of esophageal fistula and one of pneumothorax which were responded well to prolonged treatment with good results, were obtained. 6. The incidence of Klebsiella and Pseudomonas were increased recently. In these results, we submit the surgery should be performed if the conservative therapy had failed. The resection was most favorable operation for pulmonary abscess though drainage procedure may be of value in certain patients with grave systemic menifestations. In chronic long standing abscess, more complications and high mortality rate were assumable although the prognosis has been improved with the advent of antibiotics, the development of improved surgical technique and complete preoperative care.

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Characteristics of Potato Virus Y (PVY) Mutant Isolated from PVY Resistance Breeding Line in Korea (국내 감자바이러스 Y (PVY) 저항성 육성 계통에서 분리한 PVY Mutant의 특성)

  • Kim, Jae-Hyun;Kuem, Wan-Soo;Lee, Sin-Ho;Kim, Jeong-Soo;Jeon, Yong-Ho;Jung, Suk-Hun;Chung, Youl-Young;Park, Yong-Hack
    • Journal of the Korean Society of Tobacco Science
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    • v.28 no.2
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    • pp.100-110
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    • 2006
  • A mutant of Potato vims Y (PVY) was occurred in PVY resistance flue-cured tobacco breeding line KF0402 $(TC1146{\times}KF117)$ showing vein necrosis at Suwon in Korea. This isolate, PVY-SWM, was differentiated from other PVY based on biological properties and nucleotide sequence analyses of coat protein gene. PVY-SWM caused typical symptoms on 21 indicator plants as compared to the PVY-TOJC37. Remarkably, the PVY-SWM induced distinctly different symptom of systemic vein necrosis on tobacco cultivars V.SCR, PBD6, TN86, TN90, Virgin A Mutant (VAM), Wislica, NC744, KB108 and KB111, which were reported to have the recessive potyvirus resistance gene va. In RT-PCR assays with specific primers for detection of PVY, a single band of about 800bp in length was produced. The amplified DNA was cloned and the nucleotide sequence was determined. The coat protein gene of PVY-SWM showed 88.4%-99.0% and 92.5%-98.5% identities to the 12 different PVY isolates of Genbank Database at the nucleotide and amino acidi respectively. Multiple alignments as well as cluster dendrograms of PVY-SWM isolate revealed close phylogenetic relationship to the $PVY^{NTN}$ subgroup.

CLINICAL STUDY ON THE CONSCIOUS SEDATION WITH MIDAZOLAM INTRANASAL SPRAY (미다졸람의 비강내 분무를 이용한 의식진정에 대한 증례보고)

  • Kim, Hyun-Sik;Choi, Jung-Lim;Lee, Chang-Seop;Lee, Sang-Ho
    • Journal of the korean academy of Pediatric Dentistry
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    • v.25 no.4
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    • pp.782-787
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    • 1998
  • The treatment for pediatric dental patient has become more complex than the previous, because patients of pediatric dentistry, younger than the previous, and they were often combined with systemic disease. And, the importnace of conscious sedation has been increased by this time for this reason. In a variety of CNS depressants, newly developed imidazobenzodiazepine (midazolam) is well known as a safe and effective medicament. It has a rapid onset, minimized cardiovascular depression and various possible administering, route, so it is commonly used for the conscious sedation of pediatric dental patients. Recently, "intranasal drop-in method" draws attention for its safety, but discomfort during administration and posterior dripping through pharynx diminish its popularity. Now more advanced method for intranasal administration is introduced for conscious sedation for pediatric dental patients, it is "intranasal spray" with aerosol form of medicament. With this method, we can achieve some benefits as belows : 1. Diminished discomfort during intranasal spray than nitranasal drop-in. 2. Rapid osnet and reduction than intranasal drop-in. 3. Eliminatin of adverse reaction, such as rhinorrhea. 4. More improved behavior rating scale.

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Vitamin E Potentiates the Anti-nociceptive Effects by Intraperitoneal Administration of Lidocaine in Rats

  • Kim, Hye-Jin;Yang, Hae-Ji;Kim, Sun-Hyong;Kim, Dan-A;Kim, Seong-Ju;Park, Han-na;Ju, Jin-Sook;Ahn, Dong-Kuk
    • International Journal of Oral Biology
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    • v.41 no.4
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    • pp.191-197
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    • 2016
  • The present study was to evaluate effects of vitamin E on intravenous administration of lidocaine-induced antinociception. Experiments were carried out using male Sprague-Dawley rats. Orofacial formalin-induced nociceptive behavioral responses were used as the orofacial animal pain model. Subcutaneous injection of formalin produced significant nociceptive scratching behavior. Intraperitoneal injection of 5 and 10 mg/kg of lidocaine attenuated formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. Intraperitoneal injection of 1 g/kg of vitamin E also attenuated the formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. However, low dose of vitamin E (0.5 g/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. The present study also investigated effects of intraperitoneal injection of both vitamin E and lidocaine on orofacial formalin-induced behavioral responses. Vehicle treatment affected neither formalin-induced behavioral responses nor lidocaine-induced antinociceptive effects. However, intraperitoneal injection of 0.5 g/kg of vitamin E enhanced the lidocaine-induced antinociceptive effects in the 2nd phase compared to the vehicle-treated group. Intraperitoneal injection of naloxone, an opioid receptor antagonist, did not affect antinociception produced by intraperitoneal injections of both vitamin E and lidocaine. These results suggest that treatment with vitamin E enhances the systemic treatment with lidocaine-induced antinociception and reduces side effects when systemically treated with lidocaine. Therefore, the combined treatment with vitamin E and lidocaine is a potential therapeutic for chronic orofacial pain.

Simple sequence repeat marker development from Codonopsis lanceolata and genetic relation analysis

  • Kim, Serim;Jeong, Ji Hee;Chung, Hee;Kim, Ji Hyeon;Gil, Jinsu;Yoo, Jemin;Um, Yurry;Kim, Ok Tae;Kim, Tae Dong;Kim, Yong-Yul;Lee, Dong Hoon;Kim, Ho Bang;Lee, Yi
    • Journal of Plant Biotechnology
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    • v.43 no.2
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    • pp.181-188
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    • 2016
  • In this study, we developed 15 novel polymorphic simple sequence repeat (SSR) markers by SSR-enriched genomic library construction from Codonopsis lanceolata. We obtained a total of 226 non-redundant contig sequences from the assembly process and designed primer sets. These markers were applied to 53 accessions representing the cultivated C. lanceolata in South Korea. Fifteen markers were sufficiently polymorphic, and were used to analyze the genetic relationships between the cultivated C. lanceolata. One hundred three alleles of the 15 SSR markers ranged from 3 to 19 alleles at each locus, with an average of 6.87. By cluster analysis, we detected clear genetic differences in most of the accessions, with genetic distance varying from 0.73 to 0.93. Phylogenic analysis indicated that the accessions that were collected from the same area were distributed evenly in the phylogenetic tree. These results indicate that there is no correlative genetic relationship between geographic areas. These markers will be useful in differentiating C. lanceolata genetic resources and in selecting suitable lines for a systemic breeding program.

Empowerment and Ethical Sensitivity of Nurse in the Hospital (간호사의 임파워먼트와 윤리적 민감성)

  • Park, Jee-Won;You, Mi-Ae;Seo, Ye-Suk;Kim, Young-Soon
    • Journal of Korean Academy of Nursing Administration
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    • v.10 no.4
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    • pp.485-493
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    • 2004
  • Purpose: This study was to identify the degree of empowerment and ethical sensitivity of staff nurses and to examine the relationship between empowerment and ethical sensitivity. Method: Data were collected from 235 staff nurses in 4 hospitals in Gyeonggi Province using a questionnaire and collected data was analyzed by the SPSS PC program. Results: The degree of empowerment was 2.76(${\pm}$ .35) out of a possible score of 4 and that of ethical sensitivity was 0.71(${\pm}$ .11) out of a possible score of 1. The relationship of between empowerment and ethical sensitivity showed statistically significant positive correlation(r=.34, p=.00). For general characteristics, there was a significant difference in empowerment according to age(F=13.18, p=.00), educational background(t=-2.09, p=.04) and clinical practice career(F=15.15, p=.00) and in ethical sensitivity according to age(F=4.01, p=.02). In characteristics related to ethics, there was a significant difference in empowerment according to experience of ethics instruction in clinical practice(t=2.25, p=.03), attitude toward the nursing profession(F=7.96, p=.00) and ethical standards(F=9.39, p=.00) and in ethical sensitivity according to attitude toward the nursing profession(F=2.94, p=.03). Conclusion: Findings suggest that a systemic and effective training program reflecting the above general and related ethics characteristics be developed to enhance empowerment and ethical sensitivity.

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Induction of Oral Tolerance to Japanese Cedar Pollen

  • Kim, Joung-Hoon;Mun, Yeun-Ja;Ahn, Seong-Hun;Park, Joung-Suk;Woo, Won-Hong
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.557-563
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    • 2001
  • Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10 mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total Igl level and anti-JCP IgGl level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

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